Evaluating the feasibility, effectiveness and acceptability of an active play intervention for disadvantaged preschool children : a pilot study

Australian children from disadvantaged families are at increased risk of delays in acquiring fundamental movement skills, with physical inactivity and increased risk of the potential consequences of obesity. The aims of this pilot study were to: 1) assess the fundamental movement skills of disadvantaged children; 2) evaluate the feasibility and effectiveness of adapting an existing parenting and child development program to incorporate additional weekly play activities (the intervention); and 3) examine the acceptability of the intervention. Children aged 1.5-5 years were assessed pre-intervention (n = 26) and postintervention (n = 16) over a period of 22 weeks using the gross motor component of the Peabody Developmental Motor Scales - 2nd Edition (PDMS-2) (Folio &amp; Fewell, 2000). Parents completed a demographic and environmental survey and those implementing the intervention were interviewed to assess the feasibility and acceptability of the intervention. Pre-intervention the children from disadvantaged families had locomotion, object manipulation and Gross Motor Quotient (GMQ) scores significantly below the norm-referenced standards of the PDMS-2 (p &lt; 0.05). The intervention was associated with improvements in the locomotion (8.35 to 9.5; p = 0.009), and object manipulation (8.6 to 9.6; p = 0.04) subtest scores and the GMQ scores (92.6 to 99.3; p &lt; 0.01). The intervention was deemed feasible and acceptable by those implementing the program. Low levels of physical activity in disadvantaged communities may be related to delayed acquisition of fundamental movement skills in childhood. This pilot study raises the possibility of correcting this deficit in early childhood, and improving the potential for all children to lead an active life.<br /

The effects of adrenaline in out of hospital cardiac arrest with shockable and non-shockable rhythms : findings from the PACA and PARAMEDIC-2 randomised controlled trials

Introduction Previous research suggests there may be differences in the effects of adrenaline related to the initial cardiac arrest rhythm. The aim of this study was to assess the effect of adrenaline compared with placebo according to whether the initial cardiac arrest rhythm was shockable or non-shockable. Methods Return of spontaneous circulation (ROSC), survival and neurological outcomes according to the initial arrest rhythm were compared amongst patients enrolled in the PARAMEDIC-2 randomised, placebo controlled trial. The results of the PARAMEDIC-2 and PACA out of hospital cardiac arrest trials were combined and meta-analysed. Results The initial rhythm was known for 3,929 (98.2%) in the placebo arm and 3,919 (97.6%) in the adrenaline arm. The effect on the rate of ROSC of adrenaline relative to placebo was greater in patients with non-shockable cardiac rhythms (1002/3003 (33.4%) versus 222/3005 (7.4%), adjusted OR: 6.5, (95% CI 5.6-7.6)) compared with shockable rhythms 349/716 (48.7%) versus (208/702 (29.6%), adjusted OR: 2.3, 95%CI: 1.9-2.9)). The adjusted odds ratio for survival at discharge for non-shockable rhythms was 2.5 (1.3, 4.8) and 1.3 (0.9, 1.8) for shockable rhythms (P value for interaction 0.065) and 1.8(0.8-4.1) and 1.1 (0.8-1.6) respectively for neurological outcome at discharge (P value for interaction 0.295). Meta-analysis found similar results. Conclusion Relative to placebo, the effects of adrenaline ROSC are greater for patients with an initially non-shockable rhythm than those with a shockable rhythms. Similar patterns are observed for longer term survival outcomes and favourable neurological outcomes, although the differences in effects are less pronounced

Fabrication and evaluation of a micro(bio)sensor array chip for multiple parallel measurements of important cell biomarkers

© 2014 by the authors; licensee MDPI, Basel, Switzerland. This report describes the design and development of an integrated electrochemical cell culture monitoring system, based on enzyme-biosensors and chemical sensors, for monitoring indicators of mammalian cell metabolic status. MEMS technology was used to fabricate a microwell-format silicon platform including a thermometer, onto which chemical sensors (pH, O2) and screen-printed biosensors (glucose, lactate), were grafted/deposited. Microwells were formed over the fabricated sensors to give 5-well sensor strips which were interfaced with a multipotentiostat via a bespoke connector box interface. The operation of each sensor/biosensor type was examined individually, and examples of operating devices in five microwells in parallel, in either potentiometric (pH sensing) or amperometric (glucose biosensing) mode are shown. The performance characteristics of the sensors/biosensors indicate that the system could readily be applied to cell culture/toxicity studies

Growth and Antifungal Resistance of the Pathogenic Yeast, Candida Albicans, in the Microgravity Environment of the International Space Station: An Aggregate of Multiple Flight Experiences.

This report was designed to compare spaceflight-induced cellular and physiological adaptations of Candida albicans cultured in microgravity on the International Space Station across several payloads. C. albicans is a common opportunistic fungal pathogen responsible for a variety of superficial infections as well as systemic and more severe infections in humans. Cumulatively, the propensity of this organism to be widespread through the population, the ability to produce disease in immunocompromised individuals, and the tendency to respond to environmental stress with characteristics associated with increased virulence, require a better understanding of the yeast response to microgravity for spaceflight crew safety. As such, the responses of this yeast cultivated during several missions using two in-flight culture bioreactors were analyzed and compared herein. In general, C. albicans had a slightly shorter generation time and higher growth propensity in microgravity as compared to terrestrial controls. Rates of cell filamentation differed between bioreactors, but were low and not significantly different between flight and terrestrial controls. Viable cells were retrieved and cultured, resulting in a colony morphology that was similar between cells cultivated in flight and in terrestrial control conditions, and in contrast to that previously observed in a ground-based microgravity analog system. Of importance, yeast demonstrated an increased resistance when challenged during spaceflight with the antifungal agent, amphotericin B. Similar levels of resistance were not observed when challenged with the functionally disparate antifungal drug caspofungin. In aggregate, yeast cells cultivated in microgravity demonstrated a subset of characteristics associated with virulence. In addition, and beyond the value of the specific responses of C. albicans to microgravity, this report includes an analysis of biological reproducibility across flight opportunities, compares two spaceflight hardware systems, and includes a summary of general flight and payload timelines

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3 and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized Luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options

Neuroimaging in Kabuki syndrome and another KMT2D-related disorder.

Recognition of distinct phenotypic features is an important component of genetic diagnosis. Although CHARGE syndrome, Kabuki syndrome, and a recently delineated KMT2D Ex 38/39 allelic disorder exhibit significant overlap, differences on neuroimaging may help distinguish these conditions and guide genetic testing and variant interpretation. We present an infant clinically diagnosed with CHARGE syndrome but subsequently found to have a de novo missense variant in exon 38 of KMT2D, the gene implicated in both Kabuki syndrome and a distinct KMT2D allelic disorder. We compare her brain and inner ear morphology to a retrospective cohort of 21 patients with classic Kabuki syndrome and to typical CHARGE syndrome findings described in the literature. Thirteen of the 21 Kabuki syndrome patients had temporal bone imaging (5/13 CT, 12/13 MRI) and/or brain MRI (12/13) which revealed findings distinct from both CHARGE syndrome and the KMT2D allelic disorder. Our findings further elucidate the spectrum of inner ear dysmorphology distinguishing Kabuki syndrome and the KMT2D allelic disorder from CHARGE syndrome, suggesting that these three disorders may be differentiated at least in part by their inner ear anomalies